Pennsylvania Health System Research Articles

Abstract Sa1103: Utility of early Computed Tomography after out-of-hospital cardiac arrest resuscitation

Background: Initial care after out-of-hospital cardiac arrest (OHCA) poses major challenges to clinical teams due to diverse arrest etiologies and the potential need for time-sensitive interventions. Emergency department-based evaluation of these patients is crucial for identifying treatable causes of arrest. Recent data from one academic hospital highlights the potential importance of initial broad computed tomography (CT) immediately following resuscitation. Objective: To assess the ability of early post-arrest CT imaging to diagnose potential etiologies and sequelae of OHCA. Methods: We employed a registry of consecutive OHCA cases admitted to 3 hospitals within the University of Pennsylvania Health System between 1/2019-10/2020, collecting demographic, arrest, and post-arrest clinical data. Inclusion criteria included age >18 y, OHCA with return of spontaneous circulation (ROSC). We abstracted CT data including findings, contrast use, and timing, and subsequent clinical notes to assess for interventions performed based on CT findings from the EHR. KDIGO definition was used for acute kidney injury (AKI). SAS software was used for data analysis. Results: A total of 161 OHCA patients were included (mean age 60.8±15.6y; 42% female). Initial shockable rhythms were present in 16%, with 70% witnessed and 39% receiving bystander CPR. 154 patients survived to admission, and 41 survived to discharge. 117 patients underwent CT imaging in the ED: 117 underwent head CT, 87 chest CT, and 64 abdomen/pelvis CT. Median time to any first CT was 2.0h (IQR:1.4,2.8). Intracranial hemorrhage was diagnosed in 5/117 patients (4.3%); 3 received conservative therapy. Cerebral edema was found in 30/117 patients (25.6%), 10 received treatment. Pulmonary embolism was diagnosed in 8/87 cases (9.2%), 7 of which were acute and treated pharmacologically and/or mechanically. Aspiration and/or pneumonia, pneumonitis, bronchitis, bronchiolitis was found on 65/84 cases (74.7%), 30 received antibiotics. Deep venous thrombosis was detected in 3/64 patients (4.7%), 2 received anticoagulation. We found no significant differences in AKI rates with the use of contrast compared to patients receiving no contrast (p=0.93). Conclusion: These results confirm and extend other reports emphasizing the potential value for routine use of CT imaging post-ROSC. Implementing larger scale prospective studies comparing such protocols and standard-of-care is important to determine impact on OHCA outcomes.

DISP-20. SEX DIFFERENCES IN MENINGIOMA AGGRESSIVE BEHAVIOR IN RURAL POPULATIONS: A GEO-ECOLOGICAL RISK ASSESSMENT OF MENINGIOMAS IN A SINGLE RURAL HEALTH CARE SYSTEM

Abstract BACKGROUND Cause for health outcome disparities in rural populations is multifactorial. These populations are potentially more vulnerable due to rural area environmental policies and practices. Environmental justice populations (EJP) are designated by the Environmental Protection Agency as at risk for generational exposer to environmental contaminants. We assessed these population for an association between EJP density and aggressiveness of indolent brain tumors. Meningiomas are the most common benign intracranial tumor and have a female predominance. We evaluated meningioma patients in a large rural health system for oncogenic risk associated geo-ecological factors. METHODS A retrospective review of 415 pathology confirmed CNS WHO grades 1-3 meningiomas cases between 2007 – 2017 within the Geisinger Health system in Pennsylvania. Cases were mapped by county for meningioma incidence, tumor grade, and tumor recurrence. Counties were rated for EJP density. We mapped geographic areas with a higher meningioma incidence, grade, and rates of recurrence, and evaluated sex-predilections. RESULTS Seventy-three percent of tumors were WHO grade 1 (n=303), 23.4% (n=97) were grade 2, and 3.6% (n=15) were grade 3. The highest incidence of meningiomas were localized to higher density EJP counties that bordered riverbeds, Lackawanna and Luzerne. Females had a 3.5:1 predominance as compared to males. The grade 1 10-year progression free survival rate was 54.7% in Luzerne, Columbia, and Montour counties (moderate to high density EJP). Males in high EJP counties had a 12% increased risk for developing high grade meningiomas. Males aged 51-60 were more likely to develop a grade 2 or 3 meningioma as compared to males aged 61-70 in these counties. Females aged 50-60 more likely had grade 1 meningiomas but demonstrated consistently increasing risk for recurrence every decile. CONCLUSIONS Pennsylvania high density EJP counties (especially along the Lackawanna River supply) have a disproportionate risk for aggressive meningiomas and lower progression free survival as compared to national averages. A sex-discrepancy exists for males in these areas to have the most aggressive tumors.

PATH-39. AI-BASED IDENTIFICATION OF GLIOMA IDH MUTATIONAL STATUS FROM H&E-STAINED WHOLE SLIDE IMAGES

Abstract INTRODUCTION Isocitrate-dehydrogenase (IDH) mutational status is diagnostically critical in adult gliomas, with prognostic and therapeutic implications. IDH status cannot be determined by sole histologic assessment and requires molecular testing. We hypothesize that AI-based analysis can accurately predict IDH mutational status in glioma, by retrieving sub-visual cues in H&E-stained digitized tissue sections. MATERIALS AND METHODS A retrospective discovery cohort of 1,534 cases (756/778 IDH-wildtype/IDH-mutant, including all available grades) from the TCGA-LGG/TCGA-GBM collections was used for model development with 10-fold cross-validation (CV). A replication cohort of 114 cases (82/32 IDH-wildtype/IDH-mutant) from the University of Pennsylvania Health System (UPHS) was used for independent hold-out evaluation. Each 20X magnification whole slide image (WSI) underwent comprehensive curation for elimination of artifactual content, followed by partitioning into 256x256 patches, and feature extraction using pre-trained i) ImageNet weights (baseline), and ii) self-supervised vision transformer (ViT). A weakly-supervised attention-based multiple-instance-learning framework distinguished cases as IDH-wildtype or IDH-mutant, while generating visually interpretable attention heatmaps. RESULTS Evaluation on discovery and replication cohorts with the ViT yield accuracy of 90.84% (AUCDiscovery=97.16%) and 93.94% (AUCReplication=97.36%), respectively, with high sensitivity (i.e., high confidence in correctly predicting IDH-wildtype glioma). Comparison of the ViT with the baseline model on the replication cohort indicates the ViT superiority by improvements of 8% and 9.5% in accuracy and AUC, respectively. Histologic assessment of heatmaps indicates IDH-wildtype tumors exhibiting distinct regions of significant pleomorphism and microvascular proliferation, while IDH-mutant tumors exhibit dense nodular cell concentrations, microcystic architecture, and gemistocytic cells. CONCLUSION Our accurate H&E-based computational determination of glioma IDH status, with interpretations aligned with human-identifiable features, can contribute to obviating the need for molecular analyses and enable expedited diagnosis even in community healthcare settings. This study robustly identifies morpho-IDH correlates and could enable expedited patient prognostic stratification.

Clinicopathological Characteristics of Small Cell Carcinoma of the Ovary, Hypercalcemic Type – a case Series

Abstract Introduction/Objective Small cell carcinoma of the ovary hypercalcemic type (SCCOHT) is a rare (<0.01%) and aggressive ovarian tumor primarily affecting young women (median of approximately 24 years), characterized by rapid growth, early metastasis, and association with hypercalcemia in two-thirds of cases. The diagnosis of SCCOHT is challenging due to its rarity and lack of specific clinical symptoms or biomarkers. Our study aims to delineate the clinicopathologic characteristics of SCCOHT based on our case series and add to the existing knowledge. Methods/Case Report A retrospective review of University of Pennsylvania Health system pathology database was conducted from 2012 to 2024. Our study identified four patients diagnosed with SCCOHT. Clinical information and histopathologic characteristics were reviewed. Results (if a Case Study enter NA) Among the four patients identified, the median age was 24 years, with a median tumor size of 14.5 cm, and all patients presented with weight loss, abdomen bloating, and elevated CA125 levels. Notably, two patients exhibited hypercalcemia, while one initially presented with normal calcium levels but developed hypercalcemia during disease recurrence. One patient maintained normal calcium levels throughout. Surgical intervention involved bilateral salpingo-oophorectomy in all cases, with pathological staging revealing two patients at pT1a, one at pT1c, and one at pT3c. Histopathological analysis consistently revealed similar morphology, including solid and cystic necrotic neoplasms with diffuse growth or nests/cords of undifferentiated small cells, which displaying vesicular chromatin and prominent nucleoli. Immunohistochemical staining demonstrated loss of BRG1 (SMARCA4) expression in two patients and diffuse positivity for WT1 in all patietns, while negative for cytokeratin, germ cell markers, and melanocytic markers. Genetic test revealed SMARCA4 mutation (p.E 717*, c.3169-1G>A) in one patient. Conclusion Small cell carcinoma of the ovary, hypercalcemic type, presents a diagnostic and therapeutic challenge due to its rarity and aggressive nature. Adequate treatment options are currently limited, highlighting the critical need for further research and development of targeted therapies in SCCOHT. Testing for mutations in the SMARCA4 gene is essential for accurate diagnosis of SCCOHT and may uncover new avenues for treatment and management strategies.

Subsequent pregnancies in peripartum cardiomyopathy: Patient-level differences and decision-making

Study objectiveTo evaluate patient-level differences and decision making surrounding subsequent pregnancies (SSP) after peripartum cardiomyopathy (PPCM). DesignMixed methods approach to evaluate quantitative demographic and clinical differences between patients with and without a SSP and to qualitatively describe the decision-making regarding a SSP with a survey component. Setting/participants220 PPCM cases within the University of Pennsylvania Health System. Main outcome measuresDemographic, clinical and obstetrical outcomes. Results73 patients (33 %) had a SSP, 37 with a live birth. Those with a SSP were more likely to self-identify as Black (70 % vs. 52 %; p = 0.04), be nulliparous in index pregnancy (68 % vs. 45 %, p = 0.02), were younger at diagnosis (24.3 vs. 30.5 years; p < 0.01), and a higher left ventricular ejection fraction (LVEF) at diagnosis (35 % vs. 27.5 %; p = 0.03) compared to patients without a SSP. There was no difference in recovery rates of LVEF (62 % vs. 50 %, p = 0.17), or need for LVAD, transplant, or death. 22 patients completed the survey (representing 44 SSPs): 41 % of SSPs (n = 18) resulted in termination, 18 % (n = 8) in a first/s trimester loss, and 41 % (n = 18) in a live-born delivery. All patients who elected termination indicated risk of recurrence/worsening heart failure to be a motivating factor. ConclusionsLess than 20 % of patients in this single-center, multi-racial cohort had a SSP and delivery after PPCM with fear of recurrence as a large driver in this decision. Patients with a SSP were younger with a higher EF at diagnosis but ultimately had similar cardiac outcomes as patients without a SSP.

Design and rationale of penn medicine healthy heart, a randomized trial of effectiveness of a centrally organized approach to blood pressure and cholesterol improvement among patients at elevated risk of atherosclerotic cardiovascular disease

Atherosclerotic Cardiovascular Disease (ASCVD) is the leading cause of morbidity and mortality in the United States. Suboptimal control of hypertension and hyperlipidemia are common factors contributing to ASCVD risk. The Penn Medicine Healthy Heart (PMHH) Study is a randomized clinical trial testing the effectiveness of a system designed to offload work from primary care clinicians and improve patient follow-through with risk reduction strategies by using a centralized team of nonclinical navigators and advanced practice providers, remote monitoring, and bi-directional text messaging, augmented by behavioral science engagement strategies. The intervention builds on prior nonrandomized evaluations of these design elements that demonstrated significant improvement in patients' systolic blood pressure and LDL Cholesterol (LDL-C). Penn Medicine Healthy Heart will significantly improve systolic blood pressure and LDL-C compared to usual care over the 6 months of this intervention. Randomized clinical trial of Penn Medicine Healthy Heart in patients aged 35-80 years at elevated risk of ASCVD whose systolic blood pressure and LDL-C are not well controlled. The intervention consists of 4 modules that address blood pressure management, lipid management, nutrition, and smoking cessation, offered in a phased approach to give the participant time to learn about each topic, adopt any recommendations, and build a relationship with the care team. University of Pennsylvania Health System at primary care practices located in inner-city urban and rural/semi-rural areas. Improvement in systolic blood pressure and LDL-C. Cost-effectiveness analyses are planned to evaluate the health care costs and health outcomes of the intervention approach. An implementation evaluation is planned to understand factors influencing success of the intervention. 2,420 active patients of Penn Medicine primary care practices who have clinical ASCVD, or who are at elevated risk for ASCVD, and who are (a) not on statins or have LDL-C >100 despite being on statins and (b) had systolic blood pressure >140 at 2 recent ambulatory visits. March 2024-March 2025. The intervention will last 6 months with a 12-month follow-up to determine whether its effects persist. Enrolling (1,240 enrolled as of August 15, 2024) CLINICAL TRIAL REGISTRATION: NCT06062394.

Attitudes and barriers to lipoprotein(a) testing: A survey of providers at the University of Pennsylvania Health System

Guidelines recommend checking lipoprotein(a) [Lp(a)] levels in patients at high-risk for cardiovascular disease, with more recent recommendations advocating for universal screening in all adults. A brief electronic survey was distributed to select groups of University of Pennsylvania Health System (UPHS) providers, including Internal Medicine and Cardiology physicians and advance practice providers, to understand the current attitudes and barriers to testing for Lp(a). Of the 126 survey respondents, only 31 % answered that they test for Lp(a) regularly in their practice. Presence of ASCVD and a family history of ASCVD were the most common reasons for testing. Most survey respondents (69 %) replied that they do not currently check Lp(a) levels in patients. The most common reasons provided included lack of familiarity with Lp(a), insurance/ billing concerns, lack of clinical trial outcomes data, and lack of available pharmaceutical interventions. Results from ongoing clinical trials of novel Lp(a)-lowering therapies, if successful, may address provider hesitation toward Lp(a)-testing, but there remains a large gap to fill in awareness of Lp(a).

Factors Associated With Nonprescription of Oseltamivir for Infant Influenza Over 9 Seasons.

The Centers for Disease Control and Prevention (CDC) recommends oseltamivir phosphate for children <2 years old with confirmed or suspected influenza as they are at high risk for complications. We analyzed infant characteristics associated with nonprescription of oseltamivir over 9 years. We conducted a retrospective electronic health record (EHR) review of infants <12 months old born between January 1, 2012 and December 31, 2019 within the University of Pittsburgh Medical Center health system in Southwestern Pennsylvania who had >2 well-child visits during their first year. Infants with a confirmed positive test for influenza were included in the analysis. Factors associated with infant oseltamivir nonprescription were assessed using multivariable logistic regression. Of 457 infants with confirmed influenza, 86% were prescribed oseltamivir. The proportion of infants prescribed oseltamivir increased from an average of 64.6% during the 2012-2016 influenza seasons to 90.4% during the 2016-2020 influenza seasons. Infants were more likely to not be prescribed oseltamivir if they experienced >2 days of influenza symptoms (odds ratio (OR): 9.4, 95% CI: 4.8, 18.7, P < .001), were diagnosed during the 2012-2016 influenza seasons (OR: 4.2, 95% CI: 1.8, 9.5, P < .001), tested positive for influenza via a multiplex/reverse transcriptase polymerase chain reaction test (OR: 6.7, 95% CI: 2.7, 16.3, P < .001; OR: 2.7, 95% CI: 1.1, 7.1; P = .04), or did not have a fever at point-of-care (OR: 2.3, 95% CI: 1.2, 4.6, P = .01). Adherence to CDC influenza antiviral treatment guidelines for infants is high and improved over time. However, the provision of targeted education to providers may further improve oseltamivir prescribing practices for high-risk children <12 months of age.

Clinician- and Patient-Directed Communication Strategies for Patients With Cancer at High Mortality Risk

Serious illness conversations (SICs) that elicit patients' values, goals, and care preferences reduce anxiety and depression and improve quality of life, but occur infrequently for patients with cancer. Behavioral economic implementation strategies (nudges) directed at clinicians and/or patients may increase SIC completion. To test the independent and combined effects of clinician and patient nudges on SIC completion. A 2 × 2 factorial, cluster randomized trial was conducted from September 7, 2021, to March 11, 2022, at oncology clinics across 4 hospitals and 6 community sites within a large academic health system in Pennsylvania and New Jersey among 163 medical and gynecologic oncology clinicians and 4450 patients with cancer at high risk of mortality (≥10% risk of 180-day mortality). Clinician clusters and patients were independently randomized to receive usual care vs nudges, resulting in 4 arms: (1) active control, operating for 2 years prior to trial start, consisting of clinician text message reminders to complete SICs for patients at high mortality risk; (2) clinician nudge only, consisting of active control plus weekly peer comparisons of clinician-level SIC completion rates; (3) patient nudge only, consisting of active control plus a preclinic electronic communication designed to prime patients for SICs; and (4) combined clinician and patient nudges. The primary outcome was a documented SIC in the electronic health record within 6 months of a participant's first clinic visit after randomization. Analysis was performed on an intent-to-treat basis at the patient level. The study accrued 4450 patients (median age, 67 years [IQR, 59-75 years]; 2352 women [52.9%]) seen by 163 clinicians, randomized to active control (n = 1004), clinician nudge (n = 1179), patient nudge (n = 997), or combined nudges (n = 1270). Overall patient-level rates of 6-month SIC completion were 11.2% for the active control arm (112 of 1004), 11.5% for the clinician nudge arm (136 of 1179), 11.5% for the patient nudge arm (115 of 997), and 14.1% for the combined nudge arm (179 of 1270). Compared with active control, the combined nudges were associated with an increase in SIC rates (ratio of hazard ratios [rHR], 1.55 [95% CI, 1.00-2.40]; P = .049), whereas the clinician nudge (HR, 0.95 [95% CI, 0.64-1.41; P = .79) and patient nudge (HR, 0.99 [95% CI, 0.73-1.33]; P = .93) were not. In this cluster randomized trial, nudges combining clinician peer comparisons with patient priming questionnaires were associated with a marginal increase in documented SICs compared with an active control. Combining clinician- and patient-directed nudges may help to promote SICs in routine cancer care. ClinicalTrials.gov Identifier: NCT04867850.

Attitudes and Barriers to Lipoprotein(a) Testing: A Survey of Providers at the University of Pennsylvania Health System

Attitudes and Barriers to Lipoprotein(a) Testing: A Survey of Providers at the University of Pennsylvania Health System

An Integrated Approach to Address Perinatal Mental Health Within an Obstetrics Practice.

Outpatient perinatal care providers (one certified nurse-midwife, one nurse practitioner, and one physician assistant) at a high-volume, suburban health system in southeastern Pennsylvania developed and implemented a care model to identify and care for patients at risk for perinatal and postpartum mental health conditions. The program, Women Adjusting to Various Emotional States (WAVES), was created to bring the most up-to-date, evidence-based treatment recommendations to patients while addressing the increased demand placed on the health care system by pregnant and postpartum patients in need of psychiatric services. WAVES is a specialized program offered for anyone who is pregnant or up to one year postpartum who is struggling with mental health symptoms or concerns. Perinatal mood and anxiety disorders have become one of the most prevalent pregnancy ailments, yet mental health is not always addressed during routine prenatal care visits. Common obstacles to patients obtaining mental health care during pregnancy include lack of access, clinician gaps in knowledge, and stigma surrounding diagnoses. WAVES offers a method to empower perinatal providers with the education and tools to address this need. The model outlines how to appropriately assess, diagnose, manage, or refer patients for mental health services. Patient feedback has been overwhelmingly positive, and this novel care model shows great promise for the future of perinatal care. The development of integrated programs like WAVES may be a valuable resource to help combat the perinatal mental health epidemic.

The Complete Inpatient Record Using Comprehensive Electronic Data (CIRCE) project: A team‐based approach to clinically validated, research‐ready electronic health record data

AbstractIntroductionThe rapid adoption of electronic health record (EHR) systems has resulted in extensive archives of data relevant to clinical research, hospital operations, and the development of learning health systems. However, EHR data are not frequently available, cleaned, standardized, validated, and ready for use by stakeholders. We describe an in‐progress effort to overcome these challenges with cooperative, systematic data extraction and validation.MethodsA multi‐disciplinary team of investigators collaborated to create the Complete Inpatient Record Using Comprehensive Electronic Data (CIRCE) Project dataset, which captures EHR data from six hospitals within the University of Pennsylvania Health System. Analysts and clinical researchers jointly iteratively reviewed SQL queries and their output to validate desired data elements. Data from patients aged ≥18 years with at least one encounter at an acute care hospital or hospice occurring since 7/1/2017 were included. The CIRCE Project includes three layers: (1) raw data comprised of direct SQL query output, (2) cleaned data with errors removed, and (3) transformed data with standardized implementations of commonly used case definitions and clinical scores.ResultsBetween July 1, 2017 and December 31, 2023, the dataset captured 1 629 920 encounters from 740 035 patients. Most encounters were emergency department only visits (n = 965 834, 59.3%), followed by inpatient admissions without an intensive care unit admission (n = 518 367, 23.7%). The median age was 46.9 years (25th–75th percentiles = 31.1–64.7) at the time of the first encounter. Most patients were female (n = 418 303, 56.5%), a significant proportion were of non‐White race (n = 272 018, 36.8%), and 54 625 (7.4%) were of Hispanic/Latino ethnicity.ConclusionsThe CIRCE Project represents a novel cooperative research model to capture clinically validated EHR data from a large diverse academic health system in the greater Philadelphia region and is designed to facilitate collaboration and data sharing to support learning health system activities. Ultimately, these data will be de‐identified and converted to a publicly available resource.

Provider Impressions of Inpatient Teleneurology Consultation.

Teleneurology usage has increased during the severe acute respiratory syndrome coronavirus 2 pandemic. However, studies evaluating physician impressions of inpatient teleneurology are limited. We implemented a quality improvement initiative to evaluate neurologists' impression following individual inpatient teleneurology consultation at a satellite hospital of a large academic center with no in-person neurology coverage. A REDCap survey link was embedded within templates used by neurologists for documentation of inpatient consultations to be completed immediately after encounters. All teleneurology encounters with completed surveys at a single satellite hospital of the University of Pennsylvania Health System Neurology Department between May 10, 2021, and August 14, 2022, were included. Individual patient-level and encounter-level data were extracted from the medical record. A total of 374 surveys (response rate of 54.05%) were completed by 19 neurologists; 341 questionnaires were included in the analysis. Seven neurologists who specialized as neurohospitalists completed 231 surveys (67.74% of total surveys completed), while 12 non-neurohospitalists completed 110 (32.36%). The history obtained was rated as worse (14%) or the same (86%) as an in-person consult; none reported the history as better than nonteleneurology encounters. The physician-patient relationship was poor or fair in 25% of the encounters and good or excellent in 75% of visits. The overall experience was judged to be worse than in-person consultation in 32% of encounters, the same in 66%, and better in 2%. Fifty-one percent of providers responded that there were elements of the neurologic examination that might have changed their assessment and plan of care if performed in-person. Encounters with peripheral or neuromuscular-related chief complaints had the most inadequate examinations and worse overall experiences, while the most positive impressions of these clinical experiences were observed among seizure-related chief complaints. Determining best practices for inpatient teleneurology should consider the patient chief complaint to use teleneurology in scenarios with the highest likelihood of a positive experience. Further efforts should be made to the patient experience and to improve the remote examination to enhance the applicability of teleneurology to the full spectrum of inpatient neurologic consultations.

INUDGE: Integration of liquid biopsy based next generation gene sequencing in newly diagnosed NSCLC—A stepped wedge cluster randomized clinical trial.

TPS8664 Background: The development of targeted therapies has changed the treatment paradigm for non–small cell lung cancer (NSCLC). With the growing number of FDA approved targeted therapies, current NCCN guidelines recommend comprehensive molecular genotyping prior to first line (1L) therapy for all newly diagnosed patients with metastatic non-squamous (mNSq) NSCLC to enable the delivery of personalized therapy. Based on prior work that found improved detection of clinically actionable alterations through concurrent plasma (P) based next-generation gene sequencing (NGS) and tissue NGS, we piloted a behavioral economics (BE) informed electronic health record (EHR)-based “nudge” intervention designed to facilitate P NGS at the new patient medical oncology visit. After implementing across 3 practices within the University of Pennsylvania Health System (UPHS), our findings demonstrated that EHR-based nudges are feasible and can promote guideline concordant diagnostic testing at both community and academic sites (1). Methods: Design: NCT05853887 is a prospective stepped wedge cluster randomized trial that includes 3 “clusters”, representing 6 community-based cancer centers. The primary objective of this trial is to test the effectiveness of a BE informed EHR nudge intervention to increase availability of comprehensive molecular test results before 1L therapy by incorporating concurrent tissue and plasma-based molecular testing. Secondary objectives include evaluation of contextual mechanisms contributing to the adoption, reach, and effectiveness of EHR nudge interventions with a lens for health equity. Intervention: An EHR-based nudge that allows for default order placement of P NGS testing at the time of the first medical oncology visit will be implemented. Subsequently, results detected on the default P NGS order will be conveyed to providers in the form of an electronic clinical decision support notification. Statistical Methods:Sample size is based on estimates of the proportion of patients undergoing comprehensive molecular testing prior to 1L. A sample of 3 clusters in a complete stepped-wedge cluster-randomized design with 4 time periods (including the baseline), 3 steps, 1 cluster(s) switching from control to treatment at each step, and an average of 120 subjects per cluster with an average of 30 subjects per cluster per time period (for a total sample size of 360 subjects) will provide 80% power to detect a difference between proportions of 0.21701. Patients with histological, or cytological diagnosis of Stage IV mNSq NSCLC who have not yet received systemic treatment for metastatic disease are eligible for inclusion. Enrollment is ongoing: Cluster 1 began enrollment in June 2023, Cluster 2 in October 2023, and Cluster 3 is planned for February 2024. 1. Aggarwal C et al, JCO, Vol 40, Num 16, Suppl Jun 2022. Clinical trial information: NCT05853887 .

Barriers to enrollment in clinical trials in gynecologic oncology.

e13511 Background: While clinical trials improve survival in gynecologic oncology, racial and ethnic minorities remain underrepresented. Our objective was to evaluate factors associated with enrollment among patients considered for trials at a tertiary care center to inform future participant recruitment. Methods: We conducted a retrospective cohort study at the University of Pennsylvania Health System from 1/1/2022-12/31/2022. Our primary objective was the referral rate to clinical trials of patients discussed at a weekly multi-disciplinary tumor board. Patients could be discussed more than once and referred for screening for multiple trials. Each contact was classified as ‘referred/not referred’ for trial(s) screening and ‘enrolled/not-enrolled’ on trial(s). We collected socio-demographic, cancer, trial screening, and enrollment data, including reasons for ineligibility or non-enrollment, from electronic health records. We compared patient factors across 3 subgroups: 1) not-referred, 2) referred not-enrolled, 3) referred and enrolled. We performed descriptive analyses to characterize patient cohorts. Results: In a one-year period, 264 patients—194 unique—were discussed at tumor board. Referral rate for trial screening was 57%, representing 135 trial referrals for 111 unique patients. Patients were referred to screening for 2.2 trials on average. The median age of patients discussed was 65 years (IQR 58-73 years). 65.0% self-identified as White, 24.7% Black, and 10.3% other race. 96% identified English as their preferred language. The majority had Medicare insurance (51.0%), followed by private insurance (32.5%), and Medicaid (14.4%). Of 111 patients referred for trial screening, 12 patients enrolled in a trial for a referral-to-enrollment rate of 10.8% (12/111) and an overall enrollment rate of 6.2%. The majority of enrolled patients were white (10/12) and had Medicare (66%) or private insurance (25%). Cancer type varied by referral status, with most referrals for ovarian (n=87, 64%) and uterine cancer (n=37, 27.4%) and 5 for cervical cancer (3.7%). The non-referred cohort had lower rates of ovarian cancer (49.6%) and higher rates of cervical (12.4%) and other cancers (14.0%). Of patients referred to trial, but not enrolled, only 33.7% had a documented reason for non-enrollment. Documentation for incomplete screening or ineligibility cited the patient opting out of screening (26), medical comorbidity (22), and pursuit of other trial (16). Conclusions: While 57% of tumor board patients were referred for screening for at least one clinical trial, only 10.8% of referred patients and 6.2% of patients overall were enrolled in a trial. Disparities by race and insurance type were apparent between patients enrolled and not enrolled on trial. Improving documentation, educating patients about trials early in their disease course, and less restrictive trial criteria may help improve minority enrollment rates in clinical trials.

A Qualitative Study Identifying the Potential Risk Mechanisms Leading to Hospitalization for Patients With Chronic Lung Disease

BackgroundCare management programs for chronic lung disease attempt to reduce hospitalizations, yet have not reliably attained this goal. A key limitation of many programs is that they target patients with characteristics associated with hospitalization risk but do not specifically modify the mechanisms that lead to hospitalization. Research QuestionWhat are the common mechanisms underlying known patient-level risk characteristics leading to hospitalizations for acute exacerbations of chronic lung disease? Study Design and MethodsWe conducted a qualitative study of patients admitted to the University of Pennsylvania Health system with acute exacerbations of chronic lung disease between January and September 2019. We interviewed patients, their family caregivers, and their inpatient and outpatient clinicians about experiences leading up to the hospitalization. We analyzed the interview transcripts using triangulation and abductive analytic methods. ResultsWe conducted 69 interviews focused on the admission of 22 patients with a median age of 66 years (interquartile range 60 to 70), of whom 16 (73%) were women and 14 (64%) were Black. We interviewed 22 patients, 14 caregivers, 19 inpatient clinicians, and 14 outpatient clinicians. We triangulated the available interview data for each patient admission and identified the underlying mechanisms of how several known patient characteristics associated with risk actually led to hospitalization. These mechanisms included limited capacity for home management of acute symptom changes, barriers to accessing care, chronic functional limitations, and comorbid behavioral health disorders. Importantly, many of the clinical, social, and behavioral mechanisms underlying hospitalizations were present for months or years prior to the symptoms that prompted inpatient care. InterpretationCare management programs should be built to target specific clinical, social, and behavioral mechanisms that directly lead to hospitalization. Upstream interventions that reduce hospitalization risk are possible given that many contributory mechanisms are present for months or years before the onset of acute exacerbations.

Microorganisms inside healthy human organs, are the internal tissues sterile?

The recognition of microorganisms inhabiting the gut, urogenital system, skin, and lungs of humans has become widely accepted. Various studies provide evidence of microbial infiltration in tumor tissues, underscoring the potential role of the microbiome in cancer progression. Recent scientific inquiries challenge the traditional belief in the sterility of normal internal human tissues, presenting compelling findings about the existence of microbial communities within diverse internal organs. This perspective, though relatively unexplored, aligns with research in other species, such as mice. To delve deeper into the microbial presence in healthy human internal tissues, an analysis was conducted on 13,871 normal RNA-seq samples from 28 tissues obtained from the Genotype-Tissue Expression (GTEx) consortium. Acknowledging certain limitations within the GTEx analysis pipeline, it remains noteworthy that the GTEx consortium provides the most extensive and analytically robust dataset about RNA expression within healthy human tissues. Each sample's sequencing reads, not aligning with the human genome (assembly T2T-CHM13v2.0), underwent analysis using AGAMEMNON, an algorithm for aligning and quantifying microorganism abundance at various taxonomic levels. Reference database included 4034 bacterial, 489 archaea, and 11,259 viral genomes, along with 81 fungal transcriptomes. After cumulative sum scaling (CSS) normalization on species-level microbial abundances and retaining only species present in at least 10% of the samples for each tissue, gradient-boosting machine learning models were trained for each tissue. These models aimed to distinguish each tissue from all others based solely on their microbial profile. To validate the results, 38 healthy living tissue samples (from NCBI project PRJEB4337) were analyzed, as the GTEx samples were derived from post-mortem biopsies. The machine learning models exhibited robust performance for 11 out of 28 tissues (Muscle, Heart, Salivary Gland, Brain, Stomach, Colon, Small Intestine, Testis, Blood, Liver, and Bladder). Among these, 8 models demonstrated resilience to in silico contamination. The presence of resilient tissue-specific microbial signatures implies that microbial colonization is not a random occurrence. Testing the ML models on the external dataset of the 38 healthy living samples revealed high discriminatory performance for the Heart, Liver and Colon tissue, indicating the presence of a tissue-specific microbiome even in a living state for these tissues. Notably, the most crucial feature in the heart model was the fungus Sporisorium graminicola, for the colon model the gram-positive bacterium Flavonifractor plautii, and for the liver model was the gram-negative bacterium Bartonella machadoae. The presence of a distinct microbial signature within human internal organs, allowing differentiation of distinct organs through machine learning models, supports the assertion that even under healthy conditions, human internal organs host low-biomass microbial communities specific to each tissue. "BioCancer", “Bioradio 4”. University of Pennsylvania HEALTH SYSTEM (UPenn School of Medicine RedOnc), “Decision support systems to address Nosocomial Infections and Antimicrobial Resistance (MDR-CDSS).”. ‘Competitiveness, Entrepreneurship and Innovation’ [NSRF 2014 —2020], Greece. This is the full abstract presented at the American Physiology Summit 2024 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.

Text Message-Based Assessment of 90-Day Modified Rankin Scale After Stroke.

The modified Rankin Scale (mRS) is commonly used to measure disability after stroke, traditionally assessed through telephone or in-person evaluation. Here, we investigated the validity of mRS assessment through an automated text messaging system based on the simplified mRS questionnaire as an alternative method to traditional methods of assessment. A total of 250 patients admitted to 3 hospitals within the University of Pennsylvania Health System with ischemic or hemorrhagic stroke were enrolled. Participants received automated text messages sent 48 hours before their outpatient appointment at about 90 days after stroke. The mRS scores were assigned on the basis of participant responses to 2 to 4 text questions eliciting yes/no responses. The mRS was then evaluated in person or by telephone interview for comparison. Responses were compared with κ. A total of 142 patients (57%) completed the study. The spontaneous response rate to text messages was 46.5% and up to 72% with an additional direct in-person or phone call reminder. Agreement was substantial (quadratic-weighted κ=0.87 [95% CI, 0.83-0.89]) between responses derived from the automated text messaging and traditional interviews. Agreement for distinguishing functional independence (mRS 0-1) from dependence (mRS 2-5) was substantial (unweighted κ=0.79 [95% CI, 0.69-0.90]). An automated text messaging system is a feasible method for remotely obtaining the mRS after stroke and a potential alternative to traditional in-person or telephone assessment. Further studies are needed to evaluate the generalizability of text message-based approaches to stroke outcome measurement.

Radio-anatomical evaluation of clinical and radiomic profile of multi-parametric magnetic resonance imaging of de novo glioblastoma multiforme

BackgroundGlioblastoma (GBM) is a fatal, fast-growing, and aggressive brain tumor arising from glial cells or their progenitors. It is a primary malignancy with a poor prognosis. The current study aims at evaluating the neuroradiological parameters of de novo GBM by analyzing the brain multi-parametric magnetic resonance imaging (mpMRI) scans acquired from a publicly available database analysis of the scans.MethodsThe dataset used was the mpMRI scans for de novo glioblastoma (GBM) patients from the University of Pennsylvania Health System, called the UPENN-GBM dataset. This was a collection from The Cancer Imaging Archive (TCIA), a part of the National Cancer Institute. The MRIs were reviewed by a single diagnostic radiologist, and the tumor parameters were recorded, wherein all recorded data was corroborated with the clinical findings.ResultsThe study included a total of 58 subjects who were predominantly male (male:female ratio of 1.07:1). The mean age with SD was 58.49 (11.39) years. Mean survival days with SD were 347 (416.21) days. The left parietal lobe was the most commonly found tumor location with 11 (18.96%) patients. The mean intensity for T1, T2, and FLAIR with SD was 1.45E + 02 (20.42), 1.11E + 02 (17.61), and 141.64 (30.67), respectively (p = < 0.001). The tumor dimensions of anteroposterior, transverse, and craniocaudal gave a z-score (significance level = 0.05) of − 2.53 (p = 0.01), − 3.89 (p < 0.001), and 1.53 (p = 0.12), respectively.ConclusionThe current study takes a third-party database and reduces physician bias from interfering with study findings. Further prospective and retrospective studies are needed to provide conclusive data.

Health system implementation of the PROMIS Cognitive Function Screener in the Medicare Annual Wellness Visit: framing as abilities versus concerns

BackgroundCognitive assessment is a required component of the Medicare Annual Wellness Visit (AWV). In this prospective study, we evaluated acceptability and usefulness of a patient-reported outcome measure (the PROMIS® Cognitive Function Screener, or PRO-CS) to screen for cognitive impairment during the AWV. We compared two versions of the PRO-CS: Abilities and Concerns.MethodsWe developed PRO-CS Abilities and PRO-CS Concerns using items from the PROMIS Cognitive Function item banks. We partnered with a large health system in Pennsylvania to implement an electronic health record (EHR)-integrated version of the 4-item PRO-CS into their AWV workflow. PRO-CS Abilities was implemented in June 2022 and then replaced with PRO-CS Concerns in October 2022. We used EHR data to evaluate scores on Abilities versus Concerns and their association with patient characteristics. We gathered feedback from providers on experiences with the PRO-CS and conducted cognitive interviews with patients to evaluate their preferences for Abilities versus Concerns.ResultsBetween June 2022 and January 2023, 3,088 patients completed PRO-CS Abilities and 2,614 patients completed PRO-CS Concerns. Mean T-scores for Abilities (54.8) were slightly higher (indicating better cognition) than for Concerns (52.6). 10% of scores on Abilities and 13% of scores on Concerns indicated concern for cognitive impairment (T-score < 45). Both Abilities and Concerns were associated with clinical characteristics as hypothesized, with lower scores for patients with cognitive impairment diagnoses and those requiring assistance with instrumental activities of daily living. Abilities and Concerns had similar negative correlations with depression (r= -0.31 versus r= -0.33) and anxiety (r= -0.28 for both), while Abilities had a slightly stronger positive correlation with self-rated health (r = 0.34 versus r = 0.28). In interviews, providers commented that the PRO-CS could be useful to facilitate conversations about cognition, though several providers noted potential limitations of patient self-report. Feedback from patients indicated a preference for PRO-CS Concerns.ConclusionsOur findings suggest potential utility of the PRO-CS for cognitive screening in the Medicare AWV. PRO-CS Abilities and Concerns had similar associations with patient clinical characteristics, but the Concerns version was more acceptable to patients.